The asymmetric reduction of polar unsaturated bonds allows the production of valuable chiral secondary alcohols and amines for use as chiral building blocks in industry and academia. Chiral alcohols and amines that are produced by the asymmetric hydrogenation or asymmetric transfer hydrogenation of ketones and imines, respectively, are extensively used in the synthesis of pharmaceuticals, agricultural chemicals, fragrances and materials.
In the biotechnology and pharmaceutical sectors, the ability to synthesize enantiomerically pure small molecules, amino acids, peptides and proteins is of great value. The use of a drug molecule as a single enantiomer reduces the risk of side effects, increases efficacy and accuracy of dosage, and often reduces the dosage required. Further, selective synthesis of the desired enantiomer results in a reduction in cost by reducing waste. In the agrochemical business about 25% of the members of several classes of pesticides and herbicides exist as enantiomers. Volatile, enantiomerically pure alcohols are also particularly valuable in the flavours and fragrances industries where each enantiomer provides a distinctive olfactory sensation. Single enantiomer helical molecules can also impart important optical, electronic and magnetic properties to materials and nanomaterials with applications in electronic switches, motors, sensors, polarizers and displays.
One method of carrying out an asymmetric catalytic reduction is to utilize a transition metal complex. (Handbook of Homogeneous Hydrogenation, de Vries, J. G., Elsevier, C. J., Eds., Wiley-VCH: Weinheim, Germany, 2007, Vol. 3, pp 1131-1163; Minnaard, A. J., Feringa, B. L., Lefort, L., de Vries, J. G. Acc. Chem. Res. 2007, 40, 1267-1277; Malacea, R., Poli, R., Manoury, E. Coord. Chem. Rev. 2010, 254, 729-752; Ikariya, T., Blacker, A. J. Acc. Chem. Res. 2007, 40, 1300-1308; Genet, J. P. Acc. Chem. Res. 2003, 36, 908-918; Noyori, R., Ohkuma, T. Angew. Chem. Int. Ed. 2001, 40, 40-73; Modern Reduction Methods, Andersson, P. G., Munslow, I. J., Eds., Wiley-VCH: Weinheim, Germany, 2008.) Another method of carrying out an asymmetric catalytic reduction is to utilize enzymes. (Ringenberg, M. R., Ward, T. R. Chem. Commun. 2011, 47, 8470-8476; Bogar, K.; Martin-Matute, B., Backvall, J. E. Beilstein J. Org. Chem. 2007, 3, No. 50; Servi, S., Tessaro, D., Pedrocchi-Fantoni, G. Coord. Chem. Rev. 2008, 252, 715-726; Matsuda, T., Yamanaka, R., Nakamura, K. Tetrahedron: Asym. 2009, 20, 513-557.)
Classical methods for the synthesis of chiral products involve the use of a reagent from the chiral pool or the resolution of a mixture of enantiomers. Both of these methods have drawbacks, including the necessity for expensive reagents, the generation of waste, and the requirement for costly work-up. Other methods including the use of organocatalysts (Organocatalytic enantioselective reduction of olefins, ketones, and imines Kagan, H. B., Eds. Wiley-VCH: New York, 2007; Li, D., He, A. Y., Falck, J. R. Org. Letters 2010, 12, 1756-1759) and other metal-free compounds (Chase, P. A., Jurca, T., Stephan, D. W. Chem. Commun. 2008, 1701-1703; Chase, P. A., Welch, G. C., Jurca, T., Stephan, D. W. Angew. Chem. Int. Ed. 2007, 46, 8050-8053; Stephan, D. W., Erker, G. Angew. Chem. Int. Ed. 2009, 49, 46-76.) are being developed to offer cheaper and more environmentally friendly alternatives. (Blaser, H. U., Malan, C., Pugin, B., Spindler, F., Steiner, H., Studer, M. Adv. Synth. Catal. 2003, 345, 103-151; Naud, F., Spindler, F., Rueggeberg, C. J., Schmidt, A. T., Blaser, H. U. Org. Process Res. Dev. 2007, 11, 519-523; Asymmetric Catalysis on Industrial Scale: Challenges, Approaches and Solutions, Blaser, H. U., Federsel, H. J., Eds., Wiley-VCH: Weinheim, Germany, 2010.)
Complexes containing platinum group metals (PGMs) such as Pt, Ru, Rh and Ir, and chiral ligands are especially active and have been developed to be highly enantioselective. (Handbook of Homogeneous Hydrogenation de Vries, J. G., Elsevier, C. J., Eds., Wiley-VCH: Weinheim, Germany, 2007, Vol. 3, pp 1131-1163; Malacea, R., Poli, R., Manoury, E. Coord. Chem. Rev. 2010, 254, 729-752; Hedberg, C. and Gladiali, S., Taras, R. In Modern Reduction Methods Andersson, P. G., Munslow, I. J., Eds., Wiley-VCH: Weinheim, Germany, 2008: Chapter 5-6, pp 109-152; Johnson, N. B., Lennon, I. C., Moran, P. H., Ramsden, J. A. Acc. Chem. Res. 2007, 40, 1291-1299; Xie, J. H.; Zhu, S. F.; Zhou, Q. L. Chem. Rev. 2011, 111, 1713-1760.)
The information gained from mechanistic studies on these catalytic systems greatly assists in the optimization and scaling-up of the process for industrial application (For recent reviews see: Clapham, S. E., Hadzovic, A., Morris, R. H. Coord. Chem. Rev. 2004, 248, 2201-2237; Samec, J. S. M., Backvall, J. E., Andersson, P. G., Brandt, P. Chem. Soc. Rev. 2006, 35, 237-248; Sandoval, C. A., Bie, F. S., Matsuoka, A., Yamaguchi, Y., Naka, H., Li, Y. H., Kato, K., Utsumi, N., Tsutsumi, K., Ohkuma, T., Murata, K., Noyori, R. Chem. Asian J. 2010, 5, 806-816; Soni, R., Cheung, F. K., Clarkson, G. C., Martins, J. E. D., Graham, M. A., Wills, M. Org. Biomol. Chem. 2011, 9, 3290-3294; Takebayashi, S., Dabral, N., Miskolzie, M., Bergens, S. H. J. Am. Chem. Soc. 2011, 133, 9666-9669; Blaser, H. U., Malan, C., Pugin, B., Spindler, F., Steiner, H., Studer, M. Adv. Synth. Catal. 2003, 345, 103-151; Asymmetric Catalysis on Industrial Scale: Challenges, Approaches and Solutions Blaser, H. U., Federsel, H. J., Eds. Wiley-VCH: Weinheim, Germany, 2010; Johnson, N. B., Lennon, I. C., Moran, P. H., Ramsden, J. A. Acc. Chem. Res. 2007, 40, 1291-1299; Ager, D. J.; de Vries, A. H. M.; de Vries, J. G. Chem. Soc. Rev. 2012, 41, 3340-3380.) However, there are some negative features of these catalytic systems, such as high cost, low availability, and high toxicity of the metal, that make them undesirable for some applications.
Recent developments to overcome these drawbacks involve the use of first row transition metals for asymmetric catalysis. Low-valent iron is an especially attractive candidate for this role, since it is inexpensive, abundant, and non-toxic in comparison to ruthenium. Iron-containing catalysts for asymmetric reduction reactions are proving to be promising. (Junge, K., Schroder, K., Beller, M. Chem. Commun. 2011, 47, 4849-4859; Morris, R. H. Chem. Soc. Rev. 2009, 38, 2282-2291; Bauer, G., Kirchner, K. A. Angew. Chem. Int. Ed. 2011, 50, 5798-5800; Mancheno, O. G. Angew. Chem. Int. Ed. 2011, 50, 2216-2218.)
A need remains for alternative iron-containing catalytic systems for direct hydrogenation (Casey, C. P., Guan, H. R. J. Am. Chem. Soc. 2007, 129, 5816-5817; Sui-Seng, C., Freutel, F., Lough, A. J., Morris, R. H. Angew. Chem. Int. Ed. 2008, 47, 940-943; Langer, R., Leitus, G., Ben-David, Y., Milstein, D. Angew. Chem. Int. Ed. 2011, 50, 2120-2124) and transfer hydrogenation (Mikhailine, A. A., Lough, A. J., Morris, R. H. J. Am. Chem. Soc 2009, 131, 1394-139; Meyer, N.; Lough, A. J., Morris, R. H. Chem. Eur. J. 2009, 15, 5605-5610; Morris, R. H. Chem. Soc. Rev. 2009, 38, 2282-2291; Lagaditis, P. O., Lough, A. J., Morris, R. H. Inorg. Chem. 2010, 49, 10057-10066; Mikhailine, A. A., Morris, R. H. Inorg. Chem. 2010, 49, 11039-11044; Lagaditis, P. O., Lough, A. J., Morris, R. H. J. Am. Chem. Soc. 2011, 133, 9662-9665; Sues, P. E., Lough, A. J., Morris, R. H. Organometallics 2011, 30, 4418-4431; Enthaler, S., Erre, G., Tse, M. K., Junge, K., Beller, M. Tetrahedron Lett. 2006, 47, 8095-8099; Enthaler, S., Hagemann, B., Erre, G., Junge, K., Beller, M. Chem. Asian J. 2006, 1, 598-604; Furuta, A., Nishiyama, H. Tetrahedron Lett. 2008, 49, 110-113; Buchard, A., Heuclin, H., Auffrant, A., Le Goff, X. F., Le Floch, P. Dalton Trans. 2009, 1659-1667; Naik, A., Maji, T., Reiser, O. Chem. Commun. 2010, 46, 4475-4477; Kandepi, V., Cardoso, J. M. S., Penis, E., Royo, B. Organometallics 2010, 29, 2777-2782) of ketone and, recently, ketimines (Zhou, S. L., Fleischer, S., Junge, K., Das, S., Addis, D., Beller, M. Angew. Chem. Int. Ed., 49, 8121-8125). Such alternative systems are preferably highly reactive and selective.
This background information is provided for the purpose of making known information believed by the applicant to be of possible relevance to the present invention. No admission is necessarily intended, nor should be construed, that any of the preceding information constitutes prior art against the present invention.